title: Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals.
abstract: OBJECTIVE
  In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes.
  
  
  METHODS
  We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of the original, as well as from additional populations.
  
  
  RESULTS
  Significant obesity associations (p < 0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p = 7.1 × 10(-7) for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p = 0.04-2.4 × 10(-7)) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMI-adjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p = 7.8 × 10(-10)) with substantial inter-ethnic heterogeneity (p = 0.003).
  
  
  CONCLUSIONS
  We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.
authors.affiliation: Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Katsuya
authors.forename: T
authors.initials: T
authors.lastname: Nabika
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: A
authors.initials: A
authors.lastname: Fujioka
authors.forename: M
authors.initials: M
authors.lastname: Isono
authors.forename: K
authors.initials: K
authors.lastname: Ohnaka
authors.forename: T
authors.initials: T
authors.lastname: Fujisawa
authors.forename: E
authors.initials: E
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Ikegami
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Yamori
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
authors.forename: R
authors.initials: R
authors.lastname: Takayanagi
authors.forename: N
authors.initials: N
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016022:Case-Control Studies; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D009765:Obesity / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C502207:MTCH2 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C530715:TMEM18 protein, human